Age of breakthroughs: The role gut bacteria play in health and disease

Thomas R. Verny, MD is a clinical psychiatrist, academic, award-winning author, public speaker, poet and podcaster. He is the author of eight books, including the global bestseller The Secret Life of the Unborn Child and 2021′s The Embodied Mind: Understanding the Mysteries of Cellular Memory, Consciousness and Our Bodies.

A recent research paper from the University of Helsinki entitled “Impacts of maternal microbiota and microbial metabolites on fetal intestine, brain, and placenta” caught my eye.

The microbiota is a unique community of about 100 trillion bacterial cells, fungi and viruses pitching their tents in our gut. Everyone’s microbiome is unique, regulated by what we eat and drink as well as many other factors such as sleep, exercise, our social relations and environment.

Not long ago, biologists used to refer disparagingly to bacteria as “bags of enzymes” but lately gut micro-organisms have gone “legit” and scientists are now enthusiastically studying their influence on human health and disease.

For example, the above-mentioned Finnish study compared fetuses of dams living in a normal environment with dams living in a germ-free, sterile environment. What they found was that the immune system and host – microbe interactions were dialed up in the fetuses of the normal environment mothers.

Similarly, genes in the brains of fetuses of the normal environment mothers associated (researchers, as a rule, say “associated” because of the presence of a multitude of unknown factors in biology or psychology experiments, so they can rarely say “caused”) with the development and functioning of the nervous system and genes in the placenta that regulate pregnancy, were activated to a larger extent than in the controls.

Male mice were more affected than female mice. There is much speculation as to why males across the board have higher morbidity and mortality rates than females. I shall deal with that question in a future column.

We are further learning that an unbalanced gut microbiome in the mother may also lead in the offspring to dysfunction in the immune system such as inflammatory bowel diseases and allergies. Mikael Niku, the lead author of the study, remarked, “Our research helps us understand the origin of such disorders, making it potentially possible in the future to enhance their prevention and treatment.” (1)

A Swedish study (we are still in Northern Europe) followed 16,440 children for 20 years. Of this cohort, 1,197 developed a neurodevelopmental disorder.

The researchers found that the children of mothers with a disrupted gut microbiome had many biological markers that are associated with increased risk of developing in the future autism spectrum disorder, ADHD, communication disorder, speech disorder or intellectual disability as well as early emerging mood and gastrointestinal problems.

This was particularly true for preterm births and mothers who were stressed, smoked, suffered of an infection or were on antibiotics. Not surprisingly, breastfeeding led to a healthier gut flora in these children with a protective effect against the above disorders.

According to Eric W Triplett, University of Florida, “The remarkable aspect of the work is that these biomarkers are found at birth in cord blood or in the child’s stool at one year of age over a decade prior to the diagnosis.” (2)

In the last decades there have been numerous studies on the transgenerational transmission of trauma, (3, 4) but very few like the one by Bridget Callaghan at UCLA that looked at the impact of adversity on women and their microbiome which, in some cases, took place even before their child was conceived. (5)

The researchers collected data on the lives of 450 pairs of mothers and children living in Singapore. The children of these mothers fell into three distinct groups in terms of their gut microbes and their experiences.

Those whose mothers suffered of anxiety when pregnant had one kind of microbiome, those whose mothers were abused or neglected all had another and children who had lived through stressful events themselves had a different microbiome composition. The study is further evidence of a long-established dictum in genetics that stress decreases diversity of the gut microbiome with negative consequences on human mental and physical health.

It’s widely acknowledged that there’s continuous two-way communication between the gut and the brain, known as the gut-microbiome-brain axis. Disruptions in the balance and function of gut microbiota, termed dysbiosis, disturb these pathways, leading to changes in the permeability of the blood-brain barrier, which in turn results in various pathological dysfunctions, including neurological, psychological and gastrointestinal disorders. (6)

The vagus nerve which connects the brain to the heart and the gut is the main highway along which constant traffic of bidirectional signals travel. In addition to the vagus nerve, complex interaction between the gut microbiome and the brain takes place by other neural, immune, and metabolic pathways. (7)

Additionally, it has been shown that psychological stress can change the composition of the gut microbiota (9), and in turn, microbiota abnormalities can influence emotional behaviour. (10)

Dysbiosis is increasingly recognized as a possible factor in the development of many psychiatric conditions. One of these is Major Depression Disorder (MDD), generally considered the leading cause of disability worldwide and associated with death and suicide more frequently than any other psychiatric or medical condition.

Studies on germ-free rodents have explored the potential causative role of microbiome abnormalities in depression. (8, 15) Following the transfer of fecal microbiota from MDD patients to antibiotic-treated rats these rats develop depressive-like behavioural and physiological symptoms. They acquire a reduced gut microbiota diversity, decreased serotonin levels and increased neurotoxic metabolites in the blood.

Studies involving the transfer of fecal microbiota from MDD patients to antibiotic-treated rats who then develop depressive-like behavioural and physiological symptoms demonstrate the pivotal role the microbiota play in health and disease.

Symbiotic microbes have been shown to alter behaviour and potentially affect the onset and/or severity of nervous system disorders, (11) regulate nutrition and metabolism (12) and are critical for the development and function of the immune system. (13, 14)

Our gut bacteria deserve more respect. They are not your enemy. If you treat them right and provide them with a diverse diet, they will work hard to keep your mind and body in tip-top condition.

References

1. Husso, A., Pessa-Morikawa, T., Lahti, L., … & Niku, M. (2023). Impacts of maternal microbiota and microbial metabolites on fetal intestine, brain, and placenta. BMC biology, 21(1), 207.

2. Ahrens, A. P., Hyötyläinen, T., Petrone, J. R., Igelström, K., George, C. D., Triplett, Eric W, Garrett, T. J., … & Ludvigsson, J. (2024). Infant microbes and metabolites point to childhood neurodevelopmental disorders. Cell, 187(8), 1853-1873.

3. Yao, Y., Robinson, A. M., et al … & Metz, G. A. (2014). Ancestral exposure to stress epigenetically programs preterm birth risk and adverse maternal and newborn outcomes. BMC medicine, 12(1), 121.

4. Lev-Wiesel, R. (2007). Intergenerational transmission of trauma across three generations: A preliminary study. Qualitative Social Work: Research and Practice, 6(1), 75-94.

5. Querdasi, F. R., Enders, C., Karnani, N., Broekman, B., Yap Seng, C., Gluckman, P. D., … & Callaghan, B. L. (2023). Multigenerational adversity impacts on human gut microbiome composition and socioemotional functioning in early childhood. Proceedings of the National Academy of Sciences, 120(30), e2213768120.

6. Sasso, J. M., Ammar, R. M., Tenchov, R., Lemmel, S., Kelber, O., Grieswelle, M., & Zhou, Q. A. (2023). Gut Microbiome – Brain Alliance: A Landscape View into Mental and Gastrointestinal Health and Disorders. ACS Chemical Neuroscience, 14(10), 1717-1763.

7. Caspani, G., Kennedy, S., Foster, J. A., & Swann, J. (2019). Gut microbial metabolites in depression: understanding the biochemical mechanisms. Microbial Cell, 6(10), 454.

8. Valles-Colomer M, Falony G, Vieira-Silva S, … Raes J. (2019). The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol. 4(4):623–632

9. Galley JD, Nelson MC, Yu Z, Dowd SE, Walter J, Kumar PS, Lyte M, Bailey MT. Exposure to a social stressor disrupts the community structure of the colonic mucosa-associated microbiota. BMC Microbiol. 2014;14:189.

10. Crumeyrolle-Arias M, Jaglin M, Naudon L, … Rabot S. (2014). Absence of the gut microbiota enhances anxiety-like behaviour and neuroendocrine response to acute stress in rats. Psychoneuroendocrinology. 42:207–17.

11. Sampson, T. R., & Mazmanian, S. K. (2015). Control of brain development, function, and behaviour by the microbiome. Cell host & microbe, 17(5), 565-576.

12. Zhang, Y. J., Li, S., Gan, R. Y., Zhou, T., Xu, D. P., & Li, H. B. (2015). Impacts of gut bacteria on human health and diseases. International journal of molecular sciences, 16(4), 7493-7519.

13. Wiertsema, S. P., van Bergenhenegouwen, J., Garssen, J., & Knippels, L. M. (2021). The interplay between the gut microbiome and the immune system in the context of infectious diseases throughout life and the role of nutrition in optimizing treatment strategies. Nutrients, 13(3), 886.

14. Grenham, S., Clarke, G.., & Dinan, T. G. et al., (2011). Brain – gut – microbe communication in health and disease. Frontiers in physiology, Gershon, Michael D (2020). How smart is the gut? Acta Physiol. 228: e13296;

15. Dinan, T. G., & Cryan, J. F. (2013). Melancholic microbes: a link between gut microbiota and depression. Neurogastroenterology & Motility, 25(9), 713-719.